Unexplained fever with consumptive syndrome in the elderly: two cases of VEXAS syndrome with inflammasome dysregulation.

The aim of this study is to investigate the inflammasome dysregulation in peripheral blood leukocytes of VEXAS patients. The constitutive and in vitro triggered activation of inflammasome in PBMC and neutrophils was analyzed in two Brazilian patients with typical UBA1 mutations, and compared with healthy donors. Our findings highlight the constitutive activation of caspase-1 in VEXAS leukocytes, accompanied by increased plasma levels of IL-18. Furthermore, upon stimulation of isolated peripheral blood mononuclear cells (PBMC) and neutrophils, we observed not only the exhaustion of NLRP3 and NLRP1/CARD8 pathways in VEXAS PBMC but also a significant increase in NLRP3-mediated NETs release in VEXAS neutrophils. These findings support previous studies on the contribution of the inflammasome to VEXAS pathogenesis, identifying at least two profoundly affected pathways (NLRP3 and NLRP1/CARD8) in VEXAS peripheral blood.

Mendonça LO ，Leal VNC ，Roa MEGV ，Barros SF ，Kalil J ，Pontillo A ... -  《-》

Polymorphisms and expression of inflammasome genes are associated with the development and severity of rheumatoid arthritis in Brazilian patients.

Addobbati C ，da Cruz HLA ，Adelino JE ，Melo Tavares Ramos AL ，Fragoso TS ，Domingues A ，Branco Pinto Duarte ÂL ，Oliveira RDR ，Louzada-Júnior P ，Donadi EA ，Pontillo A ，de Azevêdo Silva J ，Crovella S ，Sandrin-Garcia P ... -  《-》

HIV replication is associated to inflammasomes activation, IL-1β, IL-18 and caspase-1 expression in GALT and peripheral blood.

Feria MG ，Taborda NA ，Hernandez JC ，Rugeles MT ... -  《PLoS One》

Structural basis for distinct inflammasome complex assembly by human NLRP1 and CARD8.

Gong Q ，Robinson K ，Xu C ，Huynh PT ，Chong KHC ，Tan EYJ ，Zhang J ，Boo ZZ ，Teo DET ，Lay K ，Zhang Y ，Lim JSY ，Goh WI ，Wright G ，Zhong FL ，Reversade B ，Wu B ... -  《Nature Communications》

Role of inflammasome genetics in susceptibility to HPV infection and cervical cancer development.

Only a small proportion of HPV+ women develop virus-associated lesions and cervical cancer, suggesting that other factors are involved in HPV+ keratinocyte transformation. Immune response plays an important role in clearing HPV infection, and host genetic variants resulting in defective immune response have been associated with virus persistence and/or cervical cancer. Considering that genetic variations in inflammasome genes were previously associated with viral infection and cancer development, the present study investigates selected single nucleotide polymorphisms (SNPs) in inflammasome genes as a possible risk factor for HPV infection susceptibility and/or for progression to cervical cancer. 12 SNPs in seven inflammasome-related genes (NLRP1, NLRP3, NLRP6, CARD8, IL1B, IL18, TNFAIP3) were genotyped in a Brazilian HPV+ case/control cohort (n = 246/310). Multivariate analysis was performed in case/control as well as in HPV+ women stratified by the presence or severity of histologic lesion, HPV persistence, and type of virus. IL1B rs1143643 was associated with protection against HPV infection in case/control analysis. NLRP1 rs11651270 plays a protection role against HPV persistence and/or oncogenesis. NLRP3 rs10754558 and IL18 rs1834481 exert a beneficial role against HPV persistence. NLRP3 rs10754558 variant resulted significantly associated with a lower risk to be infected with a high-risk HPV. Our findings for the first time demonstrated that inflammasome genetics could affect HPV/host interaction in terms of virus susceptibility as well as of virus/persistence and cervical cancer progression. J. Med. Virol. 88:1646-1651, 2016. © 2016 Wiley Periodicals, Inc.

Pontillo A ，Bricher P ，Leal VN ，Lima S ，Souza PR ，Crovella S ... -  《-》